Paraoxonase 1 L55M Polymorphisms Research Articles

Role of PON1 L55M Gene Polymorphism in Parkinson's Disease among North Indian Population.

The role of various genetic markers including alpha synuclein, Parkin, etc., is known in the pathogenesis of Parkinson's disease (PD). Novel genetic markers including paraoxonase 1 (PON1) have also been linked to PD pathogenesis in recent studies. The PON1 L55M allele carriers may have defective clearance of environmental toxins and may result in increased susceptibility to PD. Hence, we studied the role of PON1 L55M polymorphism in PD among a North Indian population. Seventy-four PD patients and 74 age- and sex-matched controls were recruited in this hospital-based case-control study. Baseline characteristics were recorded using structured questionnaire. DNA was extracted from 3-4 ml of venous blood, followed by PCR and restriction digestion. PON1 L55M genotypes were visualized as bands: LL (177 bp), LM (177, 140 bp) and MM (140,44 bp) on 3% agarose gel. Mann-Whitney U test and Chi-squared test were used for comparing two groups of skewed and categorical variables, respectively. Measures of strength of association were calculated by binary regression analysis. P value < 0.05 was considered as significant. Parkinson's disease patients had significantly higher exposure to pesticides (12.2%; P (organophosphate exposure) < 0.001) and well water drinking (28.4%; P = 0.006) compared to controls. Frequency distribution of LL, LM, MM genotypes was 67.5% (50/74), 28.4% (21/74), and 4.1% (3/74), respectively, for cases and 72.6% (54/74), 26% (19/74) and 1.4% (1/74), respectively, for controls. PON1 L55M genotype distribution between Parkinson's disease cases and controls was not significant (P = 0.53). PON1 L55M polymorphism was not associated with PD after adjusting for confounders by binary regression analysis. There was no significant association between PON1 L55M polymorphism and PD. Larger population-based studies would be required from India before drawing any definite conclusions.

Ailesel Koroner Arter Hastalığına Yatkınlıkta Güçlü Adaylar PON1, ITGB3 ve CYP3A4 Genlerinin Hastalıkla İlişkisi ve Haplotip Analizi

Objective: Genetic predisposition is very common among the patients with coronary artery disease (CAD), a complex and multifactorial disease. Our objective was to determine the possible association between the most remarkable functional variants in the paraoxonase 1(PON1), cytochrome P450 3A4 (CYP3A4), integrin subunit beta 3 (ITGB3) genes and familial CAD. Materials and Methods: We included 117 patients diagnosed with familial CAD and 99 healthy subjects with no family history of CAD. PON1 Q192R, PON1 L55M, CYP3A4*1G and ITGB3 L33P single nucleotide polymorphisms were genotyped using the Sequenom MassARRAY system. Results: Comparison of genotype and allele frequencies in inheritance models of polymorphisms between the patient and control groups did not reveal any significant findings related to CAD. Stratified analysis by gender did also not display any association both in females and males. There was no significant difference in the frequencies of the haplotypes of the PON1 Q192R and L55M polymorphisms between the groups. Conclusions: Our findings confirmed previous studies that did not consider PON1, CYP3A4 and ITGB3 genes as risk loci. The fact that our study was conducted only in patients with familial CAD shows the originality and importance of our results.

DNA damage in a Chilean population exposed to pesticides and its association with PON1 (Q192R and L55M) susceptibility biomarker.

The active ingredients in pesticides are known to be genotoxic that can cause mutations, chromosomal aberrations, or other types of DNA damage. Early detection of genotoxicity reduces the risk of developing diseases such as cancer or suffering from reproductive disorders. In turn, the genotoxic risk depends on the intrinsic capability of the individual to metabolize and eliminate the xenobiotic from the organism. This study aimed to determine if two polymorphisms of paraoxonase-1 (PON1), which is involved in the metabolism of several organophosphate (OP) pesticides, are predictors of susceptibility to DNA damage in agricultural workers and inhabitants of rural areas chronically exposed to pesticides. A cross-sectional study was made considering three groups: agricultural workers (occupational exposure, OE, n= 85), rural inhabitants (environmental exposure, EE, n= 60), and an unexposed group conformed by people living far from agricultural areas (U, n= 33). The level of individual DNA damage was measured using the comet assay, and genotyping was done to determine the PON1 Q192R and L55M polymorphisms. Acetylcholinesterase and butyrilcholinesterase activities were also measured to determine exposure to OP. Individuals belonging to EE and OE groups displayed higher levels of DNA damage compared with U group (p< .001). OP exposure was the main predictor of genotoxicity (β=16.19; 95% CI: 1.85, 30.52), instead of PON1 polymorphisms (β=-12.20; 95% CI: -27.87, 3.48). These results confirm the genotoxic effects of pesticide exposure and suggest that the catalytic efficiency of PON1 to metabolize OP pesticides becomes negligible in individuals with a history of long-term environmental or occupational exposure to these substances.

Paraoxonase 1 (PON1) L55M and Q192R polymorphisms are not associated with chronic kidney disease in Thai individuals with type 2 diabetes.

Decreased paraoxonase 1 (PON1) activity and PON1 polymorphisms have been found to be associated with chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of the PON1 L55M and Q192R polymorphisms with CKD in T2DM, as well as their relationship with PON1 activity. A total of 166 T2DM patients, including 83 CKD patients and 83 non-CKD patients, were recruited. Biochemical parameters and paraoxonase (PONase) and arylesterase (AREase) activities were measured. The PON1 L55M and Q192R polymorphisms were analysed by a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data were analysed using the chi-square test, Student's t-test and logistic regression analysis. Total cholesterol, TGs, LDL-C and Cr were significantly higher in CKD patients than in non-CKD patients. In contrast, the estimated glomerular filtration rate (eGFR) and AREase activity were significantly lower in CKD patients than in non-CKD patients (P<.05). The genotype and allele frequencies of the PON1 L55M and Q192R polymorphisms were not significantly different between CKD and non-CKD patients. Multivariate logistic regression analysis showed no association between the PON1 L55M and Q192R polymorphisms and CKD in T2DM. In addition, among all patients, patients with the PON1 LM genotype had significantly lower PONase activity than those with the LL genotype (P<.05). Among all patients, CKD patients and non-CKD patients, those with the PON1 RR genotype had significantly higher PONase activity but lower AREase activity than patients with the QR and QQ genotypes (P<.05). PON1 activity was influenced by the PON1 L55M and Q192R polymorphisms. However, the PON1 L55M and Q192R polymorphisms may not be considered genetic biomarkers for CKD in T2DM.

Organophosphate pesticide exposure, hormone levels, and interaction with PON1 polymorphisms in male adolescents

ObjectiveTo examine the association between urinary metabolites of organophosphate (OP) pesticides and serum concentrations of thyroid and reproductive hormones in male adolescents and to assess the potential effect of interactions between OP pesticides and paraoxonase 1 (PON1) polymorphisms on hormone levels. MethodsStudy subjects (N = 117) were male 16- to 17-year-olds from the Environment and Childhood (INMA)-Granada cohort in Spain. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos/chlorpyrifos-methyl, 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), a metabolite of diazinon, and diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP), non-specific metabolites of OP pesticides, were measured in a spot urine sample from each subject and adjusted for creatinine. Levels of reproductive hormones (total testosterone [TT], estradiol [E2], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Müllerian hormone [AMH], insulin growth factor 1 [IGF-1], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), and PON1 Q192R and L55M polymorphisms were determined in blood drawn during the same clinical visit. ResultsMultiple linear regression models showed that detectable levels of TCPy were associated with an increase in DHEAS and decreases in E2, FSH, and AMH; detectable IMPy with increases in E2, DHEAS, FSH, AMH, and prolactin and decreases in SHBG and LH; and detectable DETP with marginally-significant increases in TT and TT3 and decreases in FSH, AMH, and prolactin. The effect of IMPy and DETP on DHEAS and TT levels, respectively, was higher in subjects that carried the PON1 55MM genotype, while the effect of TCPy, IMPy, and DETP on thyroid hormone levels was higher in PON1 192QR/RR or 55MM genotype carriers. ConclusionsIn male adolescents, non-occupational exposure to OP pesticides was associated with several changes in reproductive and thyroid hormone levels, and the magnitude of some associations was greater in adolescents genetically more susceptible to OP pesticide exposure who carry the PON1 55MM genotype.

Do PON1–Q192R and PON1–L55M polymorphisms modify the effects of hypoxic training on paraoxonase and arylesterase activity?

BackgroundLow levels of antioxidant paraoxonase 1 (PON1) enzyme activity, PON1–Q192R polymorphism (a glutamine (Q) to arginine (R) substitution at position 192), PON1–L55M polymorphism (a leucine (L) to methionine (M) substitution at position 55), and oxidized low-density lipoprotein (oxLDL) are risk factors for coronary heart disease. Aerobic exercise improves PON1 activity, but the effects of hypoxic exercise are yet unclear. The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms. MethodsSerum PON1 and arylesterase activities (ARE), PON1, PON3, and oxLDL protein levels (by using the enzyme-linked immunosorbent assays) were determined in an athletic group (42 trained male underwater rugby players; age = 21.7 ± 4.2 years, mean ± SD) and a control group (43 sedentary men; age = 23.9 ± 3.2 years). The polymorphisms were determined from genomic DNA samples. ResultsPON1 activity (25.1%, p = 0.052), PON3 (p < 0.001), and oxLDL (p < 0.001) of the athletic group, including most genotype groups, were higher than those of the control group. In comparison to the controls, PON1 activity levels (p = 0.005) of the PON1–Q192R homozygote QQ genotype group and PON1 activity levels (30%, p = 0.116) of the PON1–L55M homozygote LL genotype group were higher, whereas ARE activity values of athletic R allele carrier (Rc = QR + RR) (p = 0.005) and LL group (p = 0.002) were lower than the control genotype groups related to their polymorphisms. ConclusionHypoxic training can cause (1) significant oxidative stress, including oxLDL, and an antioxidant response (increase in PON1 activity and PON3), (2) differences in the activity of PON1 and ARE, which are modified by PON1–Q192R and PON1–L55M polymorphisms, respectively, and (3) improvements in PON1 activity of QQ and LL groups. However, hypoxic training can cause a disadvantage of LL and Rc groups for ARE.

Paraoxonase 1 (PON1) L55M and Q192R Polymorphisms are Associated with Type 2 Diabetes Mellitus in Southern Thai Subjects

Background: Paraoxonase 1 (PON1) plays a critical role in the prevention of cardiovascular disease, diabetes mellitus, and other chronic diseases. Objective: The aim of the present study was to investigate the association of PON1 L55M and Q192R polymorphisms with type 2 diabetes mellitus (T2DM), and pre-diabetes. Materials and Methods: The present study included 512 subjects (223 T2DM patients, 150 pre-diabetes, and 139 healthy controls) from Southern Thailand. The PON1 L55M and Q192R polymorphisms were analyzed by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) technique. Results: PON1 Q192R polymorphism showed a statistical difference in genotype frequencies between T2DM patients and healthy controls (p&lt;0.0001). Multiple logistic regression analyses after adjusting for age, gender, and BMI showed that LM and RR genotypes increased the risk for T2DM compared with LL and QQ+QR genotypes (OR 1.96; 95% CI 1.02 to 3.76, p=0.042, and OR 1.85; 95% CI 1.11 to 3.10, p=0.019, respectively). Whereas, QR, genotype was associated with decreased risk for T2DM (OR 0.240; 95% CI 0.13 to 0.45, p&lt;0.0001), and pre-diabetes (OR 0.549; 95% CI 0.30 to 0.99, p=0.048) compared with QQ genotype. Conclusion: PON1 LM and RR genotypes may be genetic risk factors for developing T2DM but QR genotype may prevent T2DM, and pre-diabetes in Southern Thai population. Keywords: PON1, Polymorphisms, Type 2 diabetes, Pre-diabetes

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and PON1 gene polymorphisms in patients with NAFLD. Materials and methods: We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the PON1 gene polymorphisms L55M, Q192R, and C-108T. Results: There was a significant difference (p < 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group (p < 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4; p = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration (p < 0.001). Conclusions: PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the PON1 L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases.

Associations between paraoxonase-1 and systemic lupus erythematosus.

The objective of this analysis was to explore associations between paraoxonase-1 levels, gene polymorphisms and systemic lupus erythematosus. Meta-analyses of paraoxonase-1 levels and Q192R and L55M and polymorphisms in systemic lupus erythematosus were conducted. Nine articles were incorporated in our meta-analysis, which uncovered that the paraoxonase-1 level was decreased in systemic lupus erythematosus compared to control (standard mean difference = -1.626, 95% confidence interval = -2.829--0.424, p = 0.008). Ethnicity-specific meta-analysis demonstrated a relation tendency between decreased paraoxonase-1 activity and lupus in Europeans (standard mean difference = -1.236, 95% confidence interval = -2.634-0.163, p = 0.083). Paraoxonase-1 activity was reduced in systemic lupus erythematosus in a single Arab and African population. Decreased paraoxonase-1 activity was found in a small sample of systemic lupus erythematosus patients (standard mean difference = -1.642, 95% confidence interval = -3.076--0.247, p = 0.021). Ethnicity-specific analysis indicated a relationship between the paraoxonase-1 55 M allele in the Arab systemic lupus erythematosus population. However, a lack of association with systemic lupus erythematosus and the paraoxonase-1 192 R allele was observed. Meta-analyses revealed reduced paraoxonase-1 activity in patients with systemic lupus erythematosus and found possible associations between systemic lupus erythematosus and paraoxonase-1 L55M polymorphism in a specific ethnic group.

Association of Serum Paraoxonase 1 Activities, Polymorphisms and Oxidative Stress in Breast Cancer Patients with Type 2 Diabetes Mellitus.

SummaryBackgroundThe aim of the study was to investigate the association of paraoxonase 1 (PON1) polymorphism, PON1/arylesterase (ARE) activity and oxidative stress index (OSI) in breast cancer (BC) patients with type 2 diabetes (DM).MethodsOur study group consisted of 30 healthy women (HV group) and 66 female BC patients. The BC patients were divided into two groups: those with (n=37) and without DM (n=29) (BDM and NBDM group). Genotyping of PON1 Q192R and L55M polymorphisms were done by polymerase chain reaction (PCR) – restriction fragment length polymorphism (RFLP) method. Serum PON1/ARE enzyme activities, total oxidant status (TOS) and total antioxidant status (TAS) were analysed by spectrophotometric method. The ratio of TOS to TAS was accepted as the oxidative stress index (OSI).ResultsPON1 Q192R genotype frequency distribution was significantly different in the BDM group compared to the NBDM group (p=0.021). When alleles distribution was examined, R and L alleles were significantly lower, Q and M alleles were significantly higher in the BDM group than in the NBDM group (p<0.001). TOS and OSI were statistically higher in BC patients than HV group (p<0.001).ConclusionsOur results suggest that PON1 gene Q and M alleles may be the risk factors predisposing formation of BC due to increased oxidant damage seen in DM. However, these statements require further confirmation with screening PON1 polymorphism in a greater number of patients with DM, and also wide range follow-up studies are necessary for the same purpose.

Effects of Paraoxonase-1 variants on course of severity and mortality of Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever caused by Crimean Congo hemorrhagic fever virus (CCHFV). Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)-binding protein which defense the body against oxidative stress. To investigate the role of the PON1 gene in CCHF, we screened the genotypes of two single nucleotide polymorphisms (Q192R [rs662] and L55M [rs854560]) in CCHF patients stratified according to course of severity and mortality by using PCR-based RFLP assay. Overall, 132 patients diagnosed as CCHF were enrolled in this study. The frequencies of the three genotypes and two alleles of Q192R and L55M polymorphisms didn't show any statistically significant differences in terms of mortality and disease severity (p > 0.05). Any statistically significant differences were not found between severe and mild and fatal and non-fatal CCHF patients according to seven composite genotypes (p > 0.05). When we analyzed the clinical characteristics of CCHF patients stratified according to PON1gene polymorphisms, any statistically significant differences were not also observed (p > 0.05). Our study showed no possible association between genotypes of PON1 gene Q192R and L55M polymorphisms and CCHF.

Changes in lipid profile parameters and PON1 status associated with L55M PON1 polymorphism, overweight and exposure to tobacco smoke

Objective: The aim of our study was to investigate the effects of paraoxonase 1 (PON1) L55M polymorphism on the enzyme’s activity and concentration in the serum as well as its association with lipid profile parameters in a group of healthy persons. We also evaluated the presence of PON1 L55M polymorphism in a group of subjects exposed to tobacco smoke and with overweight or obesity on those parameters. Methods: Analysis of L55M polymorphism was done using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (PCR – RFLP). Serum PON1 concentration and lipid profile parameters were assayed using commercial tests. PON1 activities were measured earlier elaborated procedures. Results: We observed a statistically significant difference in HDL and PON1 concentration: the highest in the LL genotype and the lowest in the MM genotype with the LM genotype having an intermediate concentration. L55M polymorphism influence on PON1 arylesterase and phosphotriesterase activity, whereas PON1 lactonase activity did not differ in all polymorphic variant groups. Exposure to tobacco smoke and overweight or obesity additionally disorder above mentioned parameters. Overweight and obesity in LM and MM genotype could be associated with higher PON1 phosphotriesterase activity. It is also possible that MM genotype could be a determinant of smoking addiction. Conclusions: L55M polymorphism, like exposure to tobacco smoke and overweight, disorders PON1 status and lipid profile parameters; therefore, it could be a crucial risk factor for the development of many metabolic disorders.

The evaluation of two genetic polymorphisms of paraoxonase 1 in patients with pulmonary embolism.

Pulmonary embolism (PE) is caused by some genetic factors for more than half patients. Paraoxonase 1 (PON1) has significant anti-oxidative and anti-inflammatory effects. According to our knowledge, there is no study researching the relation between PON 1 gene polymorphisms and PE in the literature. Therefore, it is aimed to research possible impacts of PON 1 Q192R and L55M polymorphisms on PE, considering anti-inflammatory and anti-oxidative effects of PON 1 in Turkish population. One hundred and five PE patients and one hundred and seventeen controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses for the PON1 gene Q192R and L55M polymorphisms. Any associations were not found between clinical and demographical characteristics of PE patients and the PON1 gene Q192R polymorphism; however, there were associations between surgery, chronic renal failure, and cerebrovascular disease on the history of patients and L55M polymorphism (P=.013, P=.037, and P=.031, respectively). Genotype and allele frequencies did not show any significant differences between patients and controls according to PON1 gene Q192R and L55M polymorphisms (P>.05). The results of this study suggest that there is no correlation between PE and PON 1 gene Q192R and L55M polymorphisms in the Turkish population from the Central Black Sea region. Besides, whole genotypes and alleles of Q192R and L55M are not risk factors for patients with PE in this population.

Association of PON1 gene polymorphisms with polycystic ovarian syndrome risk: a meta-analysis of case-control studies.

Evidences showed that paraoxonase 1 (PON1) gene polymorphism has an impact on women's susceptibility to polycystic ovarian syndrome (PCOS) by influencing the expression and activity of PON1. However, the effects of three PON1 polymorphisms (- 108 C>T, L55M and Q192R) on the incidence of PCOS have generated inconsistent results. Here, we conducted a meta-analysis to investigate the association between PON1 polymorphisms and PCOS risk. All eligible trials were identified via systematic searches of multiple literature databases. Outcome data were synthesized by using crude odds ratio with 95% confidence interval. Heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed. A total of 2449 cases and 1977 controls from nine studies were selected for analysis. The pooled results showed a significant association between PCOS risk and PON1 - 108 C/T polymorphism in the following genetic models [allelic, 0.72 (0.56-0.92); homozygote, 0.51 (0.32-0.82); heterozygote, 0.44 (0.25-0.78); and dominant 0.47 (0.29-0.77)]. For the PON1 192 Q/R polymorphism, a significant relationship was found in the allelic model [0.62 (0.41-0.93)] and recessive model [0.61 (0.37-0.98)]. PCOS risk was also linked to PON1 L55M polymorphism in the heterozygote model [0.62 (0.39-0.98)] and dominant model [0.63 (0.41-0.96)]. Our study has shown that PON1 - 108 C/T polymorphism might be associated with increased risk of PCOS under the allelic, homozygote, heterozygote, and dominant models. Additionally, PON1 192 Q/R and L55M polymorphisms were significantly related only in the allelic and recessive model, and in the heterozygote and dominant model, respectively.

European versus Asian differences for the associations between paraoxonase-1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus.

Many studies have examined the associations between paraoxonase‐1 (PON1) genetic polymorphisms (Q192R, rs662 and L55M, rs854560) and the susceptibility to type 2 diabetes mellitus (T2DM) across different ethnic populations. However, the evidence for the associations remains inconclusive. In this study, we performed a meta‐analysis to clarify the association of the two PON1 variants with T2DM risk. We carried out a systematic search of PubMed, Embase, CNKI and Wanfang databases for studies published before June 2017. The pooled odds ratios (ORs) for the association and their corresponding 95% confidence intervals (CIs) were calculated by a random‐ or fixed‐effect model. A total of 50 eligible studies, including 34 and 16 studies were identified for the PON1 Q192R (rs662) and L55M (rs854560) polymorphism, respectively. As for the PON1 Q192R polymorphism, the 192R allele was a susceptible factor of T2DM in the South or East Asian population (OR > 1, P < 0.05) but represented a protective factor of T2DM in European population (OR = 0.66, 95% CI = 0.45–0.98) under a heterozygous genetic model. With regard to the PON1 L55M polymorphism, significant protective effects of the 55M allele on T2DM under the heterozygous (OR = 0.77, 95% CI = 0.61–0.97) and dominant (OR = 0.80, 95% CI = 0.65–0.99) genetic models were found in the European population, while no significant associations in the Asian populations under all genetic models (P > 0.05). In summary, by a comprehensive meta‐analysis, our results firmly indicated that distinct effects of PON1 genetic polymorphisms existed in the risk of T2DM across different ethnic backgrounds.

Association of paraoxonase 1 (PON1) L55M and PON1 Q192R gene polymorphisms and risk of psoriasis.

Although there have been significant advances for clarifying the pathogenesis of psoriasis, exact pathogenic mechanism of the disease is still unknown. Oxidative stress is considered to be a new etiopathogenetic key factor in the pathogenesis of psoriasis, as a result of the studies performing the association between psoriasis and paraoxonase 1 (PON1) activity. In this study, we aimed to examine the possible associations between the both PON1 L55M and PON1 Q192R polymorphisms and psoriasis susceptibility and disease progression in Turkish population. The study group consisted of 100 unrelated patients with psoriasis and 153 unrelated healthy controls with no psoriatic lesions in their personal history or on clinical examination. Genomic DNA was extracted from peripheral leukocytes from EDTA-anticoagulated blood using the High Pure Polymerase Chain Reaction Template Preparation Kit. To identify PON1 L55M and Q192R single-nucleotide polymorphisms, genotyping was performed using commercially synthesized primers and fluorescently labeled probes and the LightCycler 480 II Real-Time Polymerase Chain Reaction System. The genotyping method was based on methods developed previously for genotyping both PON1 55 and 192 polymorphisms using LightCycler real-time polymerase chain reaction technology, which relies on fluorescence resonance energy transfer. There was no significant difference between the PON1 L55M genotype distributions and allele frequencies of the psoriasis patients and the control group. There was a statistically significant difference between distributions of the genotype or allele frequencies of the PON1 Q192R of the patient groups and control subjects (P=0.0018 and P=0.0001, respectively). PON192Q/R polymorphisms have been found to be associated with susceptibility to psoriasis. This is the first report simultaneously investigating the possible associations between the PON1 L55M and PON1 Q192R polymorphisms and psoriasis susceptibility and disease progression in Turkish population. We provide evidence that PON1 Q192R polymorphisms may have an effect on the risk of psoriasis in the Turkish population.

Association between paraoxonase-1 gene Q192R and L55M polymorphisms in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) in a population from Cairo of Egypt.

Paraoxonase-1 (PON1) is involved in the oxidative stress process that cause tissue damage observed in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). The aim of the present study was to investigate the association of PON1 Q192R and L55M polymorphisms with risk of SLE and associated APS among Egyptian sample. The study included 120 SLE patients (45 without APS and 75 with APS) and 120 healthy subjects. PON1 Q192R and L55M polymorphisms were genotyped by real-time PCR. No significant differences in Q192R genotypes or allele frequencies were found between patients and controls (p=0.5 and 0.1, respectively). The frequency of the 55M allele was significantly higher in SLE patients than in controls (66.6 vs. 43.3%), while the 55L allele was more frequent in controls (56.6%) than in patients (33.3%) (p=0.03). The LL genotype was more frequent in controls (21.6%) than in patients (10%) while M allele carrier genotypes (LM+MM) were more frequent among patients (90%) than controls (78.3%), p=0.04. Also, the 55M allele was more frequent in APS patients (73.3%) than in patients without APS (55.6%), p=0.004. M allele carrier genotypes (LM+MM) was significantly higher among APS patients (95.4%) than in non-APS patients (80%), p=0.008. Our results indicated that the PON1 L55M polymorphism associated with SLE and associated APS in a population from Cairo of Egypt, while the Q192R polymorphism plays no role in disease susceptibility. A large scale study to assess PON1 polymorphisms, PON1 activity, and markers of oxidative stress interaction is needed to clarify the role of PON-1 polymorphisms in the pathogenesis of SLE and associated APS.

Association of paraoxonase 1 (PON1) gene polymorphisms and concentration with essential hypertension

ABSTRACTHuman serum paraoxonase 1 (PON1) is carried by high-density lipoprotein in blood circulation and is shown to be effective in preventing oxidized phospholipids carried by low-density lipoprotein particles, thus it acts as an antioxidant. Polymorphism in this gene has been investigated for many metabolic diseases, but it is not thought to be a genetic risk factor for essential hypertension. The aim of this study was to determine whether there was an association between PON1 gene polymorphisms and concentration with essential hypertension. The study population was comprised of 100 patients with essential hypertension and 100 healthy controls. One promoter region [C(-108)T] and two coding region (Q192R and L55M) polymorphisms in the PON1 gene were genotyped in individuals by using the TaqMan assay. Plasma PON1 concentration in all volunteers was also measured spectrophotometrically by the enzyme-linked immunosorbent assay method. The genotype and allele frequencies of the PON1 C(-108)T polymorphism showed significant differences between the essential hypertensive and control groups (CT vs. CC: p<0.001; T allele vs. C allele: p<0.001). There was no significant difference for the PON1 L55M polymorphism between the groups, while the heterozygote genotype of the PON1 Q192R polymorphism showed significant difference (p = 0.03). The PON1 concentration was also found to be significantly lower in hypertensive patients (p < 0.001). Decline in the level of PON1 gene may be one of the main factors in the development of essential hypertension, and the PON1 C(-108)T polymorphism may have a prognostic value in the patients with essential hypertension.

Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis

Objectives Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine and arginine at position 192 and the other leucine and methionine at position 55. Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. Our study aimed to compare the effects of PON1 192, PON1 55 polymorphisms, and PON1 activity in patients with urolithiasis and controls. Materials and methods PON1’s arylesterase/paraoxonase activities and phenotype were determined in 158 stone forming cases (Group 1) and 138 non-stone forming controls (Group 2). The PON1 192 and PON1 55 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. Results Paraoxonase activity was significantly lower in Group 1 than Group 2 (112 ± 31.8 vs. 208 ± 53.1 IU/L) (p < 0.001). The PON1 L55M polymorphism was significantly higher in Group 1. The “M” allele coding for PON1 was higher in Group 1 (p < 0.001). PON1 192 RR homozygotes had significantly higher PON1 activity than QR and QQ genotypes among all the patients (p < 0.001). Conclusion The results of our study demonstrate that the PON1 55 gene “M” allele is associated with renal stone disease. Individuals possessing the “M” allele have a higher incidence of urolithiasis. The results of this study provide genetic evidence that the PON1 gene may play a role in stone formation. PON1 genotype determination may provide a tool to identify individuals who are at risk of urolithiasis.

Association between Paraoxonase 1 (PON1) Polymorphisms and the Risk of Acute Coronary Syndrome in a North African Population.

The purpose of the present study was to investigate the distribution of PON1 Q192R and L55M polymorphisms and activities in a North African population and to determine their association with cardiovascular complications. The prevalence of the QQ, QR, RR, LL, LM, and MM genotypes in the study population was 55.4%, 34.09%, 9.83%, 41.97%, 48.20%, and 9.83% respectively. The Q, R, L, and M alleles had a gene frequency of 0.755, 0.245, 0.67, and 0.33, respectively. The PON1 192 RR genotype was significantly more prevalent among ACS patients than among healthy subjects. There was a 4.33-fold increase in the risk of ACS in subjects presenting the PON1 192 RR genotype compared to those with the QQ genotype (OR=4.33; 95% CI=1.27–17.7). There was a significantly different distribution of PON1 L55M in the ACS patient groups (UA, STEMI, NSTEMI). Moreover, individuals presenting the PON1 55MM genotype present a higher risk for ACS than those with LL genotype (OR=3.69; 95% CI=1.61–11.80). Paraoxonase activities were significantly lower in coronary patients than in healthy subjects. The decrease in PON1 activity was inversely correlated with the number of concomitant risk factors for CVD (r=0.57, p<0.0001). The results of the present study suggested that the PON1 R and M alleles may play a role in the pathogenesis of cardiac ischemia in our North African population and that a decrease in PON1 activity may be a valuable marker for monitoring the development of the atherosclerosis process and the associated cardiovascular complications.